The following discussion is not an admission that anything discussed below is citable as prior art or common general knowledge.
Viral vaccines have been used to protect against diseases and improve human and animal health. Viral vaccines are already used, or are being developed, to treat infectious diseases such as: influenza, West Nile disease, dengue fever, HIV, rabies, influenza, hepatitis A, and poliovirus.
Viral vaccines may use live and attenuated viruses, or killed viruses produced by inactivating viruses after growth in cell culture. Live, attenuated viral vaccines may take advantage of weakened or attenuated strains of the virus in order to induce an immune response in the immunized animal or human. Killed virus vaccines may induce immune responses due to the presence of high concentrations of antigen present. On upon subsequent exposure to a pathogenic strain of the virus, the immunized individual is protected from disease.
Oncolytic viruses (OV) are being developed as replicating therapeutics selected or designed to preferentially grow in and kill cancer cells. Due to the self-replicating nature of OVs, the principle challenge in OV therapy is not initial saturation of all the tumors but rather efficient spreading within tumor cells upon infection of a reasonable amount of cancerous tissue. OVs may be genetically modified or selected for attenuated growth. OVs may take advantage of cellular pathways that are aberrantly regulated in cancer cells. While this limits the spread of OVs in normal host tissues, it can also blunt their natural ability to rapidly spread within and between tumors.
Examples of viruses which have been used for viral vaccines, oncolytic viruses, or both, include: influenza virus, adenovirus, vaccinia virus, dengue virus, herpes simplex virus, poliovirus, reovirus, senecavirus, rhabdoviruses, Newcastle Disease virus, moribilivirus (Measles virus) and Modified vaccinia Ankara.
It is desirable to be able to enhance virus growth ex vivo, for example when producing viruses for viral vaccines, gene therapy or as therapeutic agents such as oncolytic viruses. It is also desirable to be able to enhance virus growth in vivo, for example to enhance spreading of oncolytic viruses within tumor cells upon infection of a reasonable amount of cancerous tissue. Such enhanced growth of oncolytic virus would result in greater cytotoxicity to the cancer.
There is a need in the art to identify compounds, methods and uses that enhance virus growth, spread or cytotoxicity.